The invention is directed to processes and apparatuses for the production of chemical compounds, in particular fermentation products.
Fermentation processes are commonly employed for the preparation of chemical compounds, such as amino acids or carboxylic acids. In practice, it is usually difficult to operate such processes in an economically feasible way, because the costs of separating the fermentation products can be quite high. These high costs are caused on the one hand by the relative low concentration in which the compounds are produced, and on the other hand by the complex nature of the fermentation medium (the broth). Separation of the chemical species produced by the fermentation reactions is at present commonly achieved by one or more steps of removal of non-desired compounds from the broth, followed eventually by isolation of the desired product. In particular when organic acids are produced, after an optional concentration step, it is common practice to facilitate the separation of these acids by the addition of acids. These known procedures are inefficient and together often give rise to large amounts of waste, such as certain salts (gypsum, sodium sulphate, ammonium sulphate), organic solvents, adsorption particles, etc.
At the same time, the possibilities for producing chemical compounds via a biotechnological route are ever increasing, in particular as a result of the increased possibilities for genetic modification of micro-organisms. One of the problems that frequently occur when chemical species are produced by micro-organisms is that the production rate is suppressed after some time as a result of product inhibition (e.g. because the products are toxic in a high concentration and/or because of the equilibrium reactions involved). Also for instance in the case of production of organic acids, the pH of the broth shifts towards values below the optimal production range. To reach as high as possible product concentrations, in common practice, alkaline chemicals are added to the broth during the fermentation process. This not only results in an increase of the osmotic pressure (which is harmful for the fermentation species), but again also leads to large amounts of waste such as gypsum, ammonium sulphate, and/or sodium sulphate.
A process used for separating products from a fermentation process is electrodialysis fermentation. This process is known from e.g. Li et al. Tetrahedron 2004, 60, 655-661; WO-A-2004/046351; JP-A-63 188385; and EP-A-1 415 702. Electrodialysis is a membrane separation process for dissolved ionic species based on the transfer of ions through selective membranes under the influence of an electric field. In electrolysis process operations the formation of precipitates is highly unwanted because precipitation leads to a blocking of the membrane pores and thus disturbs the free migration of species. Electrodialysis processes thus produce a solution of the dissolved product(s) from which the product itself has to be isolated by conventional chemical separation techniques.
It would thus be highly desirable to develop techniques that are capable of removing fermentation products from the fermentor, preferably in-situ, thus without interfering (or with only very minimal interference) to the fermentation process itself. In addition, it would be desirable if such techniques can be employed relatively easily on existing fermentation facilities (retrofitting), without requiring much adaptation to the equipment. Furthermore, the present invention aims in particular at the production by fermentation and subsequent separation of carboxylic acids and amino acids, which compounds have been notoriously difficult to separate from the fermentation broth in the past.